It is noteworthy that predictive biomarkers for ICI are present in a subset of CUP patients; for instance, programmed death-ligand 1 (PD-L1) expression is found on ≥5% of cancer cells in 22.5% of cases (≥1% in 34%) and on tumor-infiltrating lymphocytes in 58.7%, while microsatellite instability-high (MSI-H) accounts for 1.8% and tumor mutational burden (TMB) ≥17 mutations per megabase occurs in 11.8%. This evidence concerns the gene CD274 and neoplasm.